There is currently no vaccine for "strep throat", which annually afflicts about 20 million persons in the US (mostly infants and children under 12 years of age). Strep throat accounts for 10 to 30 % of all clinical visits. Less frequent, but more serious diseases can result from untreated strep throat infections. A vaccine would prevent painful sore throats and reduce the use of antibiotics and loss of school or work days. The long-term goal of the project is to develop a safe, effective and economical vaccine against acute pharyngitis caused by group A streptococcal ("strep throat") infections. The immediate, short term goals to be accomplished in phase I are: 1) Optimize surface expression in Lactococcus lactis of the conserved C-repeat region (CRR) of the M6 protein of Streptococcus pyogenes; 2) Optimize vaccine dose and schedule and determine which of two recombinant strains of L. lactis will produce in mice a maximal immune response to CRR; 3) Challenge vaccinated mice with 3 different serotypes of S. pyogenes and measure protection from pharyngeal infection. The project will test in animals a unique vaccine constructed by splicing together two genes, pip and emm6c. The emm6c gene encodes part of a protein (M6) from S. pyogenes, the causative agent of "strep throat". Antibodies directed against M6 prevent strep throat infection. Pip acts as a carder for expression of M6 on the surface of the non-pathogenic bacterium, L. lactis. Mice will be vaccinated nasally with live cultures of Lactococcus that produce one of two variations of the spliced protein encoded by pip-emm6c. The immune responses against the proteins encoded by pip-emm6c will be measured in the blood and saliva. Vaccinated mice will be challenged with an infectious dose of each of 3 different serotypes of S. pyogenes. Throat cultures will be taken to measure colonization (infection) by the pathogen. The hypotheses of this project are: 1) the vaccine will produce an immune response in both the blood and the saliva to the M6 protein; and 2) this immune response will protect the vaccinated animals against infection by many different serotypes of S. pyogenes